Multisite Heart Pacing with Adjustable Number of Pacing Sites for Terminating High Frequency Cardiac Arrhythmias

ABSTRACT

High frequency cardiac arrhythmias and fibrillations are terminated by electric field pacing pulses having an order of magnitude less energy than a conventional cardioversion or defibrillation energy. The frequency and number of the pulses are selected based on a frequency analysis of a present high frequency cardiac arrhythmia or fibrillation. The energy of the pulses is selected from 1/400 to ½ of the conventional defibrillation energy, and the amplitude of the electric field pacing pulses are selected such as to activate a multitude of effective pacing sites in the heart tissue per each pacing electrode. The number and locations of the effective pacing sites in the heart tissue are regulated by the amplitude of the electric field pacing pulses, and by an orientation of the electric field of the pulses.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation-in-part (CIP) to U.S. patentapplication Ser. No. 12/040,007 filed on Feb. 29, 2008 and claimingpriority to Provisional Application No. 60/892,855, filed on Mar. 3,2007.

FIELD OF THE INVENTION

The present invention generally relates to a method of and an apparatusfor cardiac multi site pacing with an adjustable number of pacing sites.More particular, the present invention generally relates to a method ofand an apparatus for terminating paroxysmal atrial fibrillation (AF) andventricular fibrillation (VF).

BACKGROUND OF THE INVENTION

The only successful known method of terminating high frequency cardiacarrhythmias is cardioversion also known as defibrillation. Indefibrillation the heart is reset by a single high voltage and highcurrent electric shock of a high energy which is also designated as theconventional cardioversion or defibrillation energy here. Inextra-corporal defibrillation, the voltage of such an electric shocktypically amounts to about 1000 Volts, its current to about 30 Amperes,and the conventional or state of art defibrillating energy to about 360Joules. For intracardiac defibrillation, the conventional or state ofart defibrillating energy is about 5 to 20 Joules. In both cases, theelectric field during the electric shock is about 6 V/cm. A discharge ofa defibrillator in a conscious patient is painful and extremelyunpleasant. It also has potential tissue damaging effects.

Antitachycardia pacing (ATP) is a much more gentle known method. It isnot painful, because the energy of its pacing pulses is several ordersof magnitude less than the conventional cardioversion or defibrillationenergy. ATP, however, is only successful against low frequencyarrhythmias (frequency not higher than 4 Hz). Its success rate decreasesfast with increasing frequency of the arrhythmia, and high frequencycardiac arrhythmias (frequencies larger 4 Hz), and atrial fibrillation(AF) and ventricular fibrillation (VF) cannot be terminated by ATP.

Allessie M, et al., Regional control of atrial fibrillation by rapidpacing in conscious dogs. Circulation. 1991; 84:1689-1697 have tried toentrain AF, i.e. to control it by pacing pulses at a high frequency.They were successful only locally, i.e. in a small vicinity (several cm)of the pacing electrode; outside of this vicinity AF is not entrained.

An obvious solution to this problem would be to pace AF from so manysites, i.e. with so many pacing electrodes, that they cover the atriumdense enough. But many implanted pacing electrodes and their connectingwires would severely damage a contracting heart.

U.S. Pat. No. 4,996,984 issued to Sweeney discloses a method ofdefibrillating a mammal in need of defibrillation. This known methodcomprises first determining the mammal's fibrillation cycle length; andthen administering to said mammal two bursts of electrical currentdelivered sequentially to said mammal. The current of each of the burstis from about 4 Amperes to about 10 Amperes; the voltage of each burstis from about 200 Volts to about 300 Volts; the duration of each burstis from about 8 milliseconds to about 15 milliseconds; and the timingbetween the two bursts is adjusted to about 75% of the mammal'sfibrillation cycle length. The energy of each of the bursts which areadministered within the body of the mammal is reported to be as low as 3Joules. The fibrillation cycle length of a fibrillating heart isobtained using fast Fourier transformation, for example.

U.S. Pat. No. 7,418,293 issued to Sweeney discloses further reducing theelectric energy required for terminating a fibrillation event ascompared to a single pulse used for defibrillation by means of multiplepulse defibrillation. The reported minimum energy per pulse in multiplepulse defibrillation is about a quarter of the energy required fordefibrillation by means of a single pulse.

U.S. Pat. No. 7,006,867 issued to Kroll discloses a method for overdrivepacing a patient's heart using an implantable cardiac stimulation deviceconnected to the heart. The known method comprises disposing a pluralityof leads within an atrium of the heart, sensing atrial activity throughat least one of the plurality of leads, determining an overdrive pacingrate based in part on the sensed atrial activity, and delivering atrialpacing pulses to the atrium through at least one of the plurality ofleads at the overdrive pacing rate. A first one of the plurality ofleads may be coupled to the interatrial septum of the atrium, a secondone of the plurality of leads may be coupled to the sinus node of theatrium, and a third one of the plurality of leads may be coupled to theleft atrium through the coronary sinus/great vein of the patient'sheart. The known method includes multiple site sensing and/or multiplesite pacing. In one embodiment, the delivering step comprises deliveringthe atrial pacing pulses in a staggered manner, with a first pulsedelivered to a first one of the plurality of leads and a second pulsedelivered to a second one of the plurality of leads, and with apredetermined time delay defined between delivery of the first andsecond pulses.

A method of terminating high frequency arrhythmias and AF is needed thatoperates at an energy level much lower than that of conventionalcardioversion/defibrillation and that is nevertheless able to terminatearrhythmias that ATP cannot terminate. It would be highly appreciated ifthe energy level could remain below the pain threshold.

SUMMARY OF THE INVENTION

The present invention relates to a method of cardiac multi site pacingwith an adjustable number of pacing sites, the method comprisingdelivering a multitude of electric field pacing pulses to the heartwhose amplitude is selected from about 0.15 to about 1.25 V/cm such asto activate a multitude of heterogeneities naturally existing in theheart as effective pacing sites in the heart tissue by each of theelectric field pacing pulses.

The present invention satisfies a need for a technique that permits toterminate high frequency arrhythmias and, in particular, AF with a pulseenergy much smaller than that of conventionalcardioversion/defibrillation. The method of the present invention may,however, also be used in other heart pacing applications.

In a more particular aspect, the present invention relates to a methodof terminating high frequency cardiac arrhythmias and fibrillation bymultisite electric field pacing. This method comprises determining areal time Fourier spectrum of fibrillation; selecting several highestfrequencies f_i in the spectrum; selecting the pacing pulse energy inthe range 1/400-½ of the state of art defibrillation energy; selectingpacing parameters, including a number of pulses N and a pacing frequencyF, based on the several determined highest frequencies f_i in theFourier spectrum; and delivering the pulses to the fibrillating heart toterminate the arrhythmia.

The method of the present invention is designated as anti fibrillationpacing (AFP). In another more particular aspect, the present inventionrelates to an anti fibrillation pacing (AFP) method of terminating highfrequency cardiac arrhythmias and fibrillations. This method comprisesdetermining a frequency spectrum of a high frequency cardiac arrhythmiaor fibrillation of the heart; selecting a frequency of electric fieldpacing pulses based on the frequency spectrum; selecting an energy ofthe electric field pacing pulses from about 0.01 to about 1 Joules;selecting an amplitude of the electric field pacing pulses from about0.15 to about 0.5 V/cm such as to activate a multitude ofheterogeneities naturally existing in the heart as effective pacingsites in the heart tissue by each of the electric field pacing pulses;and delivering 4 to 8 of the electric field pacing pulses having theselected frequency, energy and amplitude to the heart. Here too,selecting a frequency of electric field pacing pulses based on thefrequency spectrum may particularly include selecting a frequency of theelectric field pacing pulses based on several (e.g., three) selectedhighest frequencies in a Fourier spectrum of the high frequency cardiacarrhythmia or fibrillation.

The present invention also relates to an apparatus for cardiac multisite pacing with adjustable number of pacing sites. This apparatuscomprises a pulse generator generating electric field pacing pulseswhose amplitude is selected from about 0.15 to about 1.25 V/cm such asto activate a multitude of heterogeneities naturally existing in abiological tissue as effective pacing sites by each of the electricfield pacing pulses; and a pacing electrode connected to the pulsegenerator and configured to deliver a multitude of the electric fieldpacing pulses to a heart.

The apparatus of the present invention may be realised as an implanteddevice or as an external device. Particularly it may be used for AFP.

The invention suggests to use heterogeneities naturally existing in theheart as pacing sites. Pacing from heterogeneities naturally existing inthe heart has some advantages over conventional pacing:

a multisite pacing can be achieved without connecting many electrodes tothe heart;

the number and position of pacing sites can be regulated by changing theamplitude and the direction of the electric field of the electric fieldpulses;

an energy of the electric field pulses needed for terminating highfrequency arrhythmias and AF is up to 400 times smaller than that usedin cardioversion/defibrillation.

In heart preparations, AFP terminates high frequency cardiac arrhythmiasand AF with pulses of much smaller energy than thecardioversion/defibrillating pulse, and at a much higher success ratethan conventional ATP.

Other features and advantages of the present invention will becomeapparent to one with skill in the art upon examination of the followingdrawings and the detailed description. It is intended that all suchadditional features and advantages be included herein within the scopeof the present invention, as defined by the claims.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention can be better understood with reference to the followingdrawings. The components in the drawings are not necessarily to scale,emphasis instead being placed upon clearly illustrating the principlesof the present invention. In the drawings, like reference numeralsdesignate corresponding parts throughout the several views.

FIG. 1 illustrates that the larger a size R′ of an obstacle, the largeris a depolarization e′_(max) induced near to it by an electric field.Dimensionless coordinates: Obstacle size R′=R/λ, wherein R is theobstacle size in mm, λ˜0.5 mm is the electronic constant of the tissue.Depolarization e′_(max)=e/e_(max), wherein e is the depolarization inmV, e_(max) is the depolarization near to a very large obstacle. Thedepicted data result from an analytical solution of a linearized (LR)model according to A. Pumir, V. Krinsky, Unpinning of a rotating wave incardiac muscle by an electric field. J. Theor. Biol, 199, 311-319, 1999.

FIG. 2 illustrates how to increase a number of pacing sites byincreasing an electric field (a-c), and to modify positions of pacingsites by changing a direction of the electric field (d, e).

From a) to c) the electric field is increased. a) E=0.45 V/cm—pacingfrom 1 virtual electrode or pacing site. Short arrows indicate adirection of a propagation of a pacing wave. The pacing wave looks likea moon since it is initiated near to a circular obstacle. Further awayfrom the obstacle, the pacing wave has a circular shape, as usual. b)E=0.47 V/cm—pacing from 2 virtual electrodes or pacing sites. c) E=0.58V/cm—pacing from 4 virtual electrodes or pacing sites.

Between d) and e) the direction of the electric field (long arrow) ischanged. Amplitude of the electric field is the same E=0.5 V/cm. Thedepicted results were obtained from numerical simulations of the LRmodel.

FIG. 3 illustrates how pacing from heterogeneities (virtual electrodes)removes rotating waves. t=0.04 s: R1 and R2 designate rotating waves.t=0.18 s: P designates a pacing wave emitted from a heterogeneity(depicted as a white circle partially visible in the top right corner ofthe drawing) by an electric field pulse E=1.25 V/cm. t=0.92 s: The tipof R2 approaches the front of the pacing wave and collides with it.t=0.96 s: The tip of R2 has disappeared but a new wave break is formedat the front of R1. Thus, a jump of the wave break position and of itsorientation (arrows) has been induced (compare arrows at t=0.92 s andt=0.96 s). t=1.24 s: The rotating wave R2 is terminated. R1 is in now ina position to be terminated by the same mechanism. t=1.38 s: Rotatingwaves are removed. Pacing waves emitted from the heterogeneity (a whitecircle at the upper right corner) entrain the whole medium. The depictedresults were obtained from numerical simulations of the LR model.

FIG. 4 illustrates that pacing from an ATP fixed lead does not removerotating waves. t=0.04 s: same as in FIG. 3. t=0.28 s: P designates afirst pacing wave emitted from a fixed electrode (right lower corner). Adashed line indicates a boundary of the region paced by this wave.t=0.42 s: By a second pacing wave, the size of the paced region isincreased. t=0.54 s: A third pacing wave decays. A fuzzy front is seeninstead of a sharp front observed with propagating waves. t=1.32 s: Thesize of the paced region has decreased (as compared to t=0.42 s). t=2.36s: The rotating waves are not removed. A small paced region (at thelower right corner) enlarges and shrinks quasi periodically. Thedepicted results were obtained from numerical simulations of the LRmodel. All simulation parameters were the same as in FIG. 3.

FIG. 5 is a diagram illustrating an embodiment of controlling highfrequency cardiac arrhythmias by an AFP external device. A standard ATPexternal device 5 and the AFP external device 1 according to the presentinvention are connected to a heart. The further items schematicallydepicted in FIG. 5 are a defibrillating electrode 3, a diagnosticcatheter 4, a catheter with stimulating electrodes 6, a paddleelectrode, an ECG electrode 11, and a switch 17.

FIG. 6 is a flow chart illustrating the AFP external device of FIG. 5 inmore detail. A frequency spectrum analyzer 16 transfers data to a pulseenergy selector 21 and to a pacing frequency selector 22. The itemsschematically depicted in FIG. 6 for their first time are controls 13,14 and 15 to manually set the period of the stimulating pulses, thenumber of pulses and the energy of each pulse, and a further switch 18.

FIG. 7 is a flow chart illustrating an AFP implanted device. Thefrequency spectrum analyzer 16 transfers data to a microprocessor 21,and after processing in the microprocessor the data are forwarded to apulse generating block 23. The items schematically depicted in FIG. 7for their first time are stimulating electrode 25, defibrillatingelectrode 26, and sensing electrode 27.

FIG. 8 is a frequency spectrum of a high frequency cardiac arrhythmia orfibrillation of a heart displaying three highest frequencies f_1, f_2,f_3 and a dominant frequency f_d.

FIG. 9 illustrates the dependence of the number of effective pacingsites or wave sources (WES) as a function of electric field strength E(panel b). The increase of WES with E corresponds to a decrease inactivation time, i.e. the time it takes to activate the entire hearttissue (see panel a).

DETAILED DESCRIPTION

The present invention enables pacing by electric field pulses toterminate high frequency arrhythmias. AFP permits to terminate AF and VFwith a pulse energy which is one to two orders of magnitude smaller thanthat of cardioversion or defibrillation. In AFP, numerousheterogeneities naturally existing in the heart are used as effectivepacing sites or virtual electrodes. The size distribution of naturalheterogeneities in the heart is wide: it extends from microns tomillimeters. This permits to control the number of effective pacingsites from 1 or 2 to dozens.

The basic physical mechanism exploited in AFP is well known incardiology: it is a change of membrane potential by an electric fieldnear to defects or heterogeneities. This phenomenon has been designatedas “virtual electrodes” (Sepulveda, N G, Roth, B J, Wikswo, J P. Currentinjection into a two-dimensional anisotropic bidomain. Biophys J, 55(5),987-99, 1989). Virtual electrodes are believed to play an important rolein defibrillation, exist in all tissues and thus terminate allpropagating waves. Creating a large size virtual electrode by cuttingthe cardiac tissue with a blade in order to decrease the pacingthreshold almost to a half when pacing from a small fixed wire electrodehas been proposed in U.S. Pat. No. 7,142,928.

An electric field, applied to the heart creates depolarized andhyperpolarized regions near every heterogeneity in the heart,corresponding to redistributions of the intracellular and extracellularcurrents. If the induced depolarization is above a threshold, it caninduce a propagating excitation wave. This mechanism has been used incardiology to explain how defibrillation works. The invention proposesto use this effect for creating as many effective pacing sites asneeded, from 1 or 2 to dozens, and to use them to terminatefibrillation. In experiments using cardiac muscle preparations, theinventors verified that 1 or 2 effective pacing sites were induced byone pulse having an electric field amplitude of as low as 0.15 to 0.25V/cm, 3 to 5 effective pacing sites were induced with 0.25 to 0.35 V/cm,and dozens of effective pacing sites were induced with 0.35 to 0.5 V/cm.For comparison: the electric field needed for conventionaldefibrillation is about 6 V/cm. Thus, the electric field needed toinduce dozens of effective pacing sites is more than 10 fold smallerthan the electric field needed for conventional defibrillation. Sincethe electric energy W is proportional to the square of the electricfield E (W˜E²), the electric energy per pulse is even 100 fold smallerthan the energy of a conventional defibrillation shock.

Now referring in greater detail to the drawings, FIG. 1 illustrates thatthe larger the size R′ of the obstacle the larger is the depolarizationinduced by an electric field near to it. Pulses of electric field ofsmall amplitude induce pacing only from large size heterogeneities (seeFIG. 2 a). Increasing the amplitude of the electric field results inpacing also being induced from smaller, i.e. less intense,heterogeneities and from heterogeneities of a smaller size (see FIG. 2b, c). For obstacles of generic shape (not circular), the orientation ofthe electric field affects the position and the number of the effectivepacing sites (see FIG. 2 d, e).

FIGS. 1 and 2 both demonstrate that (i) increasing the intensity of theelectric field applied in a fixed direction leads to wave emission froman increasingly large set of heterogeneities in the tissue, and that(ii) changing the direction of the applied electric field leads to waveemission from different sets of heterogeneities in the tissue. Theseaspects of the present invention permit to realize multisite heartpacing with adjustable number of effective pacing sites.

From a conventional point of view, the method of the present inventionshould not be able to terminate AF or VF due to the very low energy ofthe electric field pulses used. However, the method of the presentinvention does terminate AF and VF activating a multitude of effectivepacing sites in the heart.

In majority of biological applications of a multisite pacing, importantis to reach a desired effect, say, increase the contraction force of adamaged heart to the needed level. Then, the contraction force ismeasured. Adjusting the number of pacing sites can be achieved inseveral successive steps. If the contraction force is below the neededlevel, the electric field amplitude will be increased, and thecontraction force measured again. If the force is not enough, theelectric field amplitude will be increased again. If the force is morethan needed, the electric field amplitude will be decreased. If themeasured contraction force is enough, this electric field amplitude willbe kept. In such cases, adjusting the number of pacing sites is achievedwithout measurement the actual number of pacing sites, my measuring thebiological effect.

The actual number of activated pacing sites in the heart, may beestimated based on measuring the propagation time of a single pacingpulse to reach a detection electrode. For a fiber, wherein a pacing anddetecting electrodes are connected to the ends of the fiber, thepropagation time t_1 at which a pulse delivered by the pacing electrodereaches the detecting electrode is t_1=L/C, wherein L is the fiberlength and C is the pulse propagation velocity.

If N pacing sites are homogeneously distributed over the fiber, thedistance between the detecting electrode and the nearest pacing site isL_N=L/N. If an electric field pulse applied by the pacing electrodeactivates all pacing sites in the fiber, the propagation time t_p of apulse to reach the detecting electrode will be the propagation time fromthis nearest pacing site, i.e. t_p=L/CN (compare FIG. 9 panel a). Fromthis equitation, the number N of pacing sites can be derived as N=L/(Ct_p). For two-dimensional and three-dimensional propagation, similarformulas are easily obtained. The relation between the propagation timefrom the nearest pacing site, i.e. the activation time of the entiretissue and the number of pacing sites is a key to closed loop control ofthe number of pacing sites.

The electric field in the electric field pulses should not exceed 6V/cm. With an electric field higher than 6 V/cm, the whole heart, i.e.all of the heart tissue is excited simultaneously (6 V/cm is theelectric field value of common defibrillating), and any further increasein electric field will not increase the number of effective pacingsites.

Changing location of the pacing sites can be achieved by changingorientation of the electric field. A change of orientation of theelectric field may both be achieved by switching between a plurality ofpacing electrodes connected to the heart at different locations and byswitching between a plurality of ground electrodes which may be providedextrathoracally or even extracorporally. These ground electrodes serveas counter electrodes to the at least one pacing electrode. They may bepaddle or other large surface electrodes to keep low the current densityat the electrode surface.

In the following, the AFP method according to the present invention willbe compared to ATP.

Conventional ATP is only successful against low frequency arrhythmias,and its success rate fast decreases with increasing frequency of thearrhythmia. The physical reason for the inability of ATP to terminatehigh frequency arrhythmias is that with low frequency pacing, all pacingwaves propagate over the whole heart, but that with high frequencypacing, the propagation of the high frequency waves over the whole heartcannot be sustained.

The high frequency waves decay with increasing distance from the pacingelectrode by which they are applied to the heart. Due to the Wenckebachrhythm transformation, every second wave (more rarely, every third wave)decays generically. Thus, only near to the pacing electrode, thefrequency of the propagating waves is the frequency of the pacingpulses; at a distance to the pacing electrode, the frequency ofpropagating waves becomes lower. These low frequency waves are only ableto capture low frequency arrhythmias, but no high frequency arrhythmias.

To terminate a high frequency pathological source of waves, the pacingelectrode should be situated close to it. With conventional fixed pacingleads, this will be achieved by chance only. Pacing from cardiacheterogeneities, however, permits to regulate the number and theposition of pacing sites, and thus to avoid this problem.

FIGS. 3 and 4 numerically illustrate how, for geometrical reasons, aconventional fixed pacing lead may fail to pace away a set of rotatingwaves, whereas virtual electrodes in the tissue permits to pace away aset of rotating waves. In FIG. 3, only one heterogeneity used for pacingis shown.

An embodiment of an AFP external device 1 according to the presentinvention is schematically shown in FIG. 5 together with a defibrillator7 and an ATP external device 5. More details of the AFP external device1 according to the present invention are shown in FIG. 6. The device 1for controlling high frequency cardiac arrhythmias consists of thefollowing main parts: a pulse generating block 12, an arrhythmiafrequency spectrum analyzer 16, a pulse energy selector 21, and a pacingfrequency selector 22. Pulse generating block 12 is tuned by controldevices 13, 14, 15 to manually set the period of the pulses, the numberof pulses and the energy of a pulse. The pulse generating block 12 isconnected to a defibrillating or pacing electrode 3, to a switch 18 andto a memory 20. The Pulse generating block 12 of the AFP external device1 according to the present invention is different to that one of thecardioverter/defibrillator 7 and that one of the ATP pacemaker 5 in thatit is able to deliver pulses at time interval much shorter than usuallyneeded to charge a capacitor of the defibrillator and to pace fromdefibrillating electrodes, and in that it supplies 1 to 2 orders ofmagnitude less pulse energy than a defibrillator.

In an embodiment of the invention, the defibrillating or pacingelectrode 3 is an intracardiac catheter defibrillating electrode. Inanother embodiment of the invention, it may be an implanted intracardiacelectrode. External defibrillating patches may also be used as pacingelectrodes, but not in cases in which pacing pulses below the painthreshold are to be applied.

Pulse Energy selector 21 obtains data from an ECG/EMG amplifier 10 andis connected to the memory 20. Pacing Frequency selector 22 obtains datafrom ECG/EMG amplifier 10 and is connected to the memory 20. PacingFrequency selector 22 sends data to a monitor 19 includingrecommendations to a clinician with regard to the values to be set forthe period of the pulses, the number of pulses and the energy of apulse.

Arrhythmia frequency spectrum analyzer 16 obtains data from ECG/EMGamplifier 10 and is connected to the memory 20. Frequency spectrumanalyzer 16 is intended to (i) help to choose the pacing frequency forpacing from virtual electrodes, and (ii) protect against delivering anelectric field pulse near the T wave on the ECG.

Function (i) is needed since during AF the EMG/ECG records are notperiodic, and the choice of the pacing interval even by a well trainedmedical personnel may be erroneous. In a stationary device, the analyzeron line supplies frequencies and amplitudes of 3 largest peaks in theFourier spectrum of the arrhythmia, and the whole Fourier spectrum.

Function (ii) provides for an additional protection against induction ofVF when AFP is applied in atria. Usually, synchronization of thecardioverter/defibrillator with the R wave is used. But since AFPdelivers several electric field pulses, all of them cannot besynchronized with the R wave. Instead, the EMG/ECG automatic analyzerfor AFP protects against delivering an electric field pulse near the Twave in the ECG.

The frequency of the electric field pulses may be selected from about0.9 to about 1.1 times an arrhythmia characteristic frequency. Thischaracteristic frequency may be selected from the three largest orhighest peaks in the Fourier spectrum of the arrhythmia. Preferably, itis selected from the three peaks in the Fourier spectrum which displaythe highest frequency. These three peaks may or may not (see FIG. 8)include a dominant frequency that displays the highest amplitude in theFourier spectrum.

FIG. 7 is a block diagram of an implanted device according to thepresent invention. Pulse generating block 23 delivers pulses either viaan implanted ATP electrode 25 or from defibrillation electrodes 3. Forpacing from an implanted electrode, it chooses standard pacingamplitudes commonly applied for ATP.

For pacing from defibrillation electrodes, the pulse generating block 23allows for choosing the energy of the pulses from 0.01 J to 1 J forintracardiac defibrillating electrodes, the time interval between thepulses from 100 ms to 250 ms, and the number of pulses from 4 to 8pulses.

Pulse generating block 23 receives data from microprocessor 21 andoperates a switch 18. In an implanted device, Frequency spectrumanalyzer 16 contains several band pass filters to avoid overloading of amicroprocessor with calculations of Fourrier spectra. Frequency spectrumanalyzer 16 obtains data from sensing electrode 27 and sends data tomemory 20 and to microprocessor 21. Microprocessor 21 selects the pulseenergy and the pacing frequency and sends these data to the pulsegenerating block 23. Microprocessor 21 also operates a defibrillator 24.

An advantageous embodiment of the invention comprises an external AFPdevice which is usable for clinical investigations. AFP is applied if anarrhythmia with frequency higher than that permitting to use ATP isdetected. In cases suitable for the application of AFP, the frequency ofthe arrhythmia is above the threshold for ATP but not by more than 50%.

FIG. 5 is a block diagram illustrating an embodiment of controlling highfrequency cardiac arrhythmias by anti-fibrillation pacing (AFP) externaldevice 1. AFP External Device 1 is coupled to a patient's heart 2 via adiagnostic catheter 4 and defibrillating electrode 3, that may either bean implanted defibrillating electrode or a catheter. ATP external device5 is connected to the patient's heart 2 via a catheter 6 comprisingmonopolar or bipolar stimulating electrodes. Defibrillator 7 isconnected to the patient's chest 9 via paddle electrodes 8. ECGamplifier 10 is connected to ECG electrodes 11 via switch 17. Switch 17disconnects ECG amplifier 10 from ECG electrodes 11 when AFP externaldevice 1 delivers AFP pulses to the heart.

FIG. 6 is a block diagram illustrating AFP external device. Pulsegenerating block 12 is connected to defibrillating electrode 3. Controls13, 14, 15 are connected to pulse generating block 12. The controls 13,14, 15 permit to manually set the period or frequency of the stimulatingpulses (control 13), the number of pulses (control 14) and the electricenergy of each pulse (control 15). Frequency spectrum analyzer 16 isconnected to ECG amplifier 10 and diagnostic catheter via switch 18.Switch 18 disconnects ECG/EMG amplifier 10 from diagnostic catheter 4when Pulse generating block 12 delivers AFP pulses to the heart.

Frequency spectrum analyzer 16 selects several (e.g., 3) highestfrequencies f_i, i=1, 2, 3 from the real time arrhythmia frequencyspectrum, an exemplary example of which is depicted in FIG. 8. PacingFrequency selector 22 determines the number of pulses N and the pacingfrequency F to complete scanning of the phase spaces of 3 wave sources(rotating waves) emitting waves with frequencies f_i, to hit theirVulnerable Windows (VW) and terminate them. A skilled person can proposedifferent algorithms to achieve this. Below is an illustrative example.

Example: Calculate dT_2−1=T_2−T_1, dT_3−2=T_3−T_2, dT_3−1=T_3−T_1,wherein T_i=1/f_i, i=1, 2, 3. Calculate the minimal number of pulses Nneeded to scan the entire phase space N_1=2T_1/dT_1−2, N_2=2T_2/dT_1−2.

If 4<N _(—)1, N _(—)2<10, set F=2/(T _(—)1+T _(—)2), N=N _(—)2.

If 4≧N _(—)1, N _(—)2, set F=0.8/T _(—)1, N=5.

If N _(—)1, N _(—)2>10, calculate N _(—)3=2T _(—)3/dT _(—)3−2.

If 4<N _(—)3<10, set F=2/(T _(—)2+T _(—)3), N=N3.

If N _(—)3>10 set F=2.4/(T _(—)1+T _(—)2+T _(—)3),

N=1+T3/[0.42(T _(—)2+T _(—)3)−0.58 T _(—)1)].

If 4≧N _(—)3, set F=1.6/(T _(—)1+T _(—)2), N=1+T _(—)2/(0.625 T_(—)2−0.375 T _(—)1).

The same approach can be used for a number of highest frequency peakshigher than 3.

In an AFP implanted device, FIG. 7, frequency spectrum analyzer 16transfers data to memory 20 and microprocessor 21. Microprocessor 21selects pulse energy, pacing frequency and the number of pulses, andtransfers them to the Pulse generating block 23.

Microprocessor 21 in FIG. 7 determines several highest frequencies (f_i)from the real time frequency spectrum. Microprocessor 21 in FIG. 7selects the pacing pulse energy in the range 1/400-½ of the state of artdefibrillation energy.

Frequency spectrum analyzer 16 is connected to monitor 19 where itdisplays the Fourier spectrum of AF or other high frequency arrhythmiato help medical personnel to chose pacing frequency for ATP or AFP.Pulse generating block 12 and Frequency spectrum analyzer 16 areconnected to memory 20.

AFP External Device 1 may be realized as a box, i.e. as a single unitcontaining all these elements, or it can use an external PC as ECG/EMGanalyzer 16, memory 20 and monitor 19.

FIG. 7 is a flow chart illustrating AFP implanted device. Pulsegenerating block 23 is connected to the heart via defibrillatingelectrode 3 when it delivers AFP pacing and via stimulating electrode 25when it delivers ATP pacing. Defibrillator 24 is connected to the heartvia defibrillating electrode 26 which may be the same as thedefibrillating electrode 3. Frequency spectrum analyzer 16 is connectedto the heart via sensing electrode 27. All is controlled byMicroprocessor 21.

The AFP method of the present invention has been successfully testedagainst fibrillations both in vivo and in vitro experiments. Therequired pulse energies for terminating AF were 0.15 J in vivo and 0.08J in vitro; and the required pulse energy for terminating for VF was0.14 J in vitro. These energies are actually measured data.

Comparison of the Method of the Present Invention with Other Patents:

Kroll U.S. Pat. No. 7,809,439 B2 describes a conventional multisitepacing, i.e., for pacing from, say, 5 sites he needs 5 leads. Krolldescribes also one lead, but he uses it to pace from one site only. Hedoes not use or anticipate creation and control of several pacing siteswith one lead only.

Kroll describes fibrillation termination. He does not use the Fourrierspectrum. Kroll presents no experimental tests of his approach toarrhythmias termination, thus it is not possible to compareeffectiveness of his method with the method of the present invention.

Sweeney U.S. Pat. No. 4,996,984, U.S. Pat. No. 8,000,786 B2 describes anapproach to terminate fibrillation based on time intervals associatedwith the fibrillation cycle length. He describes also experimental testsof his approach on n=2 animals. Sweeney's minimal defibrillation energyis 2.7-3 J. The average fibrillation termination energy in the method ofthe present invention is 0.14 J, i.e. ˜20 times less (obtained on n=8animals).

Mechanism Underlying and Advantages of the Method of the PresentInvention:

The Fourier spectrum contains information about frequencies of severalfastest rotating waves. This information is needed to complete scanningof their phase spaces. Thus, the vulnerable window (VW) of every one ofthem is hit by a scanning pulse, terminating every of one them. No priorart method known to the inventors uses Fourier spectrum to selectparameters of pacing to terminate fibrillation.

More Detailed Explanation of the Mechanism:

A necessary condition to terminate a rotating wave “i” by scanning itsphase space and hitting its VW is: the pacing period T should be notclose to its rotation period T_i. The information needed for this iscontained in the Fourier spectrum.

Examples a) and b) below illustrate it:

a) For 3 selected fastest rotating waves with periods T1=90 ms, T2=100ms, T3=110 ms, if the chosen pacing period is 101 ms, then the phasespace of the wave 2 will be scanned with the scanning step t_1=101ms-100 ms=1 ms. Then, to scan the entire phase space of the wave 2, thenumber of pulses needed N_2=100 ms: 1 ms=100 pulses. Such a big numberof pulses cannot be used. But with any number of pulses N<100, thescanning of the phase space of wave 2 will not be completed. Hitting itsVW with a pacing pulse and thus termination of the rotating wave cannotbe guaranteed.

b) If the chosen pacing period is close to 90 ms, or to 110 ms, thenrequired number of pulses N_1 or N_3 will be unrealistically large. Manyvariations and modifications may be made to the preferred embodiments ofthe invention without departing substantially from the spirit andprinciples of the invention. All such modifications and variations areintended to be included herein within the scope of the presentinvention, as defined by the following claims.

1. A method of cardiac multi site pacing with an adjustable number ofpacing sites, the method comprising: delivering a multitude of electricfield pacing pulses to the heart, wherein an amplitude is selected fromabout 0.15 to about 1.25 V/cm to activate a multitude of heterogeneitiesnaturally existing in the heart as effective pacing sites in the hearttissue by each of the electric field pacing pulses.
 2. The method ofclaim 1, wherein the electric field pacing pulses are each delivered tothe heart by one pacing electrode only.
 3. The method of claim 2,wherein only one lead is directly connected to the heart for deliveringthe electric field pacing pulses to the heart.
 4. The method of claim 1,wherein a number and locations of the effective pacing sites in theheart are regulated by the amplitude of the electric field pacingpulses.
 5. The method of claim 3, further comprising: estimating anactual number of effective pacing sites; comparing the actual number ofeffective pacing sites with a required number of effective pacing sites;increasing the amplitude of the electric field pulses if the actualnumber of effective pacing sites is less than the required number ofeffective pacing sites; decreasing the amplitude of the electric fieldpulses if the actual number of effective pacing sites is larger than therequired number of effective pacing sites.
 6. The method of claim 1,wherein a number and locations of the effective pacing sites in theheart are regulated by an orientation of the electric field of theelectric field pacing pulses.
 7. The method of claim 6, wherein adirection of the electric field is changed by switching betweendifferent ground electrodes.
 8. The method of claim 6, wherein adirection of the electric field is changed by switching betweendifferent pacing electrodes.
 9. The method of claim 1, furthercomprising: determining a frequency spectrum of a high frequency cardiacarrhythmia or fibrillation of the heart; selecting a frequency of theelectric field pacing pulses based on the frequency spectrum; anddelivering the multitude of electric field pacing pulses for terminatingthe frequency cardiac arrhythmia or fibrillation.
 10. The method ofclaim 9, wherein the frequency spectrum is determined by determining areal time Fourier spectrum of the high frequency cardiac arrhythmia orfibrillation of the heart.
 11. The method of claim 9, furthercomprising:—selecting an energy of the electric field pacing pulses fromabout 0.01 to about 1 Joules.
 12. The method of claim 9, wherein theamplitude of the electric field pacing pulses is from about 0.15 toabout 0.5 V/cm.
 13. The method of claim 9, wherein the multitude of theelectric field pacing pulses delivered to the heart is from 4 to 8 ofthe electric field pacing pulses.
 14. A method of terminating highfrequency cardiac arrhythmias and fibrillation by multisite electricfield pacing, the method comprising: determining a real time Fourierspectrum of fibrillation; selecting several highest frequencies f_i inthe spectrum; selecting the pacing pulse energy of about 1/400-½ of thestate of art defibrillation energy; selecting pacing parameters,including a number of pulses N and a pacing frequency F, based on theseveral determined highest frequencies f_i in the Fourier spectrum; anddelivering the pulses to the fibrillating heart to terminate thearrhythmia.
 15. The method of claim 14, wherein the pacing frequency Fdiffers by at least about 5% from any of the determined highestfrequencies.
 16. The method of claim 14, wherein the number N of pacingpulses is selected as N=max(N_1, N_2, N_3) where N_i is the number ofpulses needed to complete scanning of the phase space of the rotatingwave with frequency f_i, and to hit its vulnerable window with at leastone pulse.
 17. The method of claim 14, wherein the number N of pacingpulses is selected as N=max(N_i, i=1, 2, . . . , n).
 18. The method ofclaim 17, wherein n=3.
 19. The method of claim 14, wherein the pacingfrequency F is chosen to minimize number N of pacing pulses, or to keepthem within 2≧N≧10.
 20. An anti fibrillation pacing (AFP) method ofterminating high frequency cardiac arrhythmias and fibrillations, themethod comprising: determining a frequency spectrum of a high frequencycardiac arrhythmia or fibrillation of the heart; selecting a frequencyof electric field pacing pulses based on the frequency spectrum;selecting an energy of the electric field pacing pulses from about 0.01to about 1 Joules; selecting an amplitude of the electric field pacingpulses from about 0.15 to about 0.5 V/cm to activate a multitude ofheterogeneities naturally existing in the heart as effective pacingsites in the heart tissue by each of the electric field pacing pulses;and delivering 4 to 8 of the electric field pacing pulses having theselected frequency, energy and amplitude to the heart.
 21. An apparatusfor cardiac multi site pacing with adjustable number of pacing sites,the apparatus comprising: a pulse generator generating electric fieldpacing pulses whose amplitude is selected from about 0.15 to about 1.25V/cm to activate a multitude of heterogeneities naturally existing in abiological tissue as effective pacing sites by each of the electricfield pacing pulses; and a pacing electrode connected to the pulsegenerator and configured to deliver a multitude of the electric fieldpacing pulses to a heart.
 22. The apparatus of claim 21, wherein thepacing electrode is selected from a defibrillating coil on a cardiacdefibrillating catheter and a patch electrode.
 23. The apparatus ofclaim 21, further comprising an estimating device estimating a number ofeffective pacing sites in the heart.
 24. The apparatus of claim 21,further comprising: an ECG/EMG amplifier; and pulse energy selectorcoupled to the ECG/EMG amplifier and to the pulse generator.
 25. Theapparatus of claim 21, further comprising at least one ground electrodeconnected to the pulse generator.
 26. The apparatus of claim 21, furthercomprising a unit configured to determine a frequency spectrum of a highfrequency cardiac arrhythmia or fibrillation of the heart.
 27. Theapparatus of claim 26, wherein the unit is configured to determine thefrequency spectrum as a real time Fourier spectrum.
 28. The apparatus ofclaim 27, wherein the unit is configured to determine several highestfrequencies in the Fourier spectrum.
 29. The apparatus of claim 28,wherein the unit includes 3 to 7 band pass filters.
 30. The apparatus ofclaim 29, further comprising a unit selecting the pacing parameters,including the number of pulses and the pacing frequency, based on thedetermined highest frequencies in the Fourier spectrum.
 31. Theapparatus of claim 21, further comprising a unit selecting the pacingpulse energy from about 1/400 to ½ of the state of art defibrillationenergy.
 32. The apparatus of claim 21, further comprising a unitselecting the pacing pulse energy from about 0.01 to about 1 Joules. 33.The apparatus of claim 21, wherein the number of the electric fieldpacing pulses in the multitude of the electric field pacing pulses isadjustable.